Plans describe the continuation of an ambitious and successful program investigating fundamental chemistry directed towards the syntheses of unique, biologically active natural products. The research plan details innovative solutions and strategies which address the challenging aspects of bond construction and stereochemistry presented by these highly functionalized marine metabolites. The program is organized into two categories. I. Macrolactone Antitumor Antibiotics. Part A: Plans for the synthesis of amphidinolide C are presented. Marine macrolides of the amphidinolide family are among the most potent antitumor agents discovered, with remarkable activity in nearly all NCI tumor cell lines. Extremely limited quantities have hampered complete structural elucidations and biological studies. The proposed chemistry develops new functionalized allylic and allenylic reagents for the efficient and stereocontrolled formation of sensitive, densely functionalized components. Studies include the extension of Pd(0)-coupling reactions in this demanding context to lead to the first synthesis of amphidinolide C. Part B: The powerful antitumor and antifungal properties of leucascandrolide A have generated considerable attention. Our asymmetric allylstannane methodology promises to deliver the most stereoselective approach yet devised for rapid construction of the alternating 1,3,5-oxygenation pattern which characterizes this unique macrolactone. II. Novel Carbocyclic Antibiotics. Part A: Studies are directed toward kendomycin, a potent antitumor quinone methide system, displaying a conformationally restricted 18-membered ansa bridge. Our strategic plan describes key oxidation chemistry of benzofurans. Ring-closing metathesis, Julia condensations, and pinacol couplings will be explored for macrocycle formation. Diels-Alder reactions will examine opportunities for synthesis of complex 1-arylpyrans as a generalized approach toward C-arylglycosides. Methodology for preparation of contiguous stereotriads will utilize allenylstannanes. Part B: Efforts toward the synthesis of nine-membered, cytotoxic marine xenicanes will investigate strategies for rapid construction of these conformationally constrained carbocycles from functionalized acyclic precursors. A thematic presentation of ring formation strategies and developments for Pd(0) chemistry fuel these efforts. The selective synthesis of contiguous stereotriads will advance basic methodology for asymmetric conjugate additions.